Tumor cell dissemination reflects the collective outcome of multiple events that include the invasion of the cancer cells into the surrounding stroma, subsequently their intravasation and entrance into circulation, and ultimately their extravasation and seeding into the sites of secondary growth. It is conceivable that interference with the pathways that promote the dissemination of the cancer cells will inhibit metastases providing tools for disease management. Directed cell migration towards specific gradients of chemoattractive factors may provide a model to explain the spread of cancer cells and the initiation of the metastatic process. While this mechanism appears attractive in explaining cancer cell dissemination, details remain elusive, and useful treatment protocols based upon the mechanism likewise remain elusive.
Chemokines are a superfamily of small, cytokine-like proteins that are resistant to hydrolysis, promote neovascularization or endothelial cell growth inhibition, induce cytoskeletal rearrangement, activate or inactivate lymphocytes, and mediate chemotaxis through interactions with G-protein coupled receptors. Chemokines can mediate the growth and migration of host cells that express their receptors.
CCL8 is a small cytokine belonging to the CC chemokine family that attracts monocytes, lymphocytes, basophils and eosinophils. The processed form (generally referred to as MCP-2) is understood to activate many different immune cells, including mast cells, eosinophils and basophils implicated in allergic responses, and monocytes, T cells, and NK cells that are involved in the inflammatory response, and inhibits the chemotactic effect most predominantly of CCL7, but also of CCL2 and CCL5. CCL8 elicits its effects by binding to several different chemokine cell surface receptors including CCR1, CCR2B and CCR5. CCL8 can bind heparin and is believed to play a role in neoplasia and inflammatory host responses.
What are needed in the art are methods and materials for prevention of tumor cell dissemination. Methods and materials for use in aggressive cancers, such as triple-negative breast cancers would be of great benefit.